CDK9 directs H2B monoubiquitination and controls replication-dependent histone mRNA 3'-end processing

EMBO Rep. 2009 Aug;10(8):894-900. doi: 10.1038/embor.2009.108. Epub 2009 Jul 3.

Abstract

Post-translational histone modifications have essential roles in controlling nuclear processes; however, the specific mechanisms regulating these modifications and their combinatorial activities remain elusive. Cyclin-dependent kinase 9 (CDK9) regulates gene expression by phosphorylating transcriptional regulatory proteins, including the RNA polymerase II carboxy-terminal domain. Here, we show that CDK9 activity is essential for maintaining global and gene-associated levels of histone H2B monoubiquitination (H2Bub1). Furthermore, CDK9 activity and H2Bub1 help to maintain correct replication-dependent histone messenger RNA (mRNA) 3'-end processing. CDK9 knockdown consistently resulted in inefficient recognition of the correct mRNA 3'-end cleavage site and led to increased read-through of RNA polymerase II to an alternative downstream polyadenylation signal. Thus, CDK9 acts to integrate phosphorylation during transcription with chromatin modifications to control co-transcriptional histone mRNA processing.

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Line
  • Cell Line, Tumor
  • Chromatin Immunoprecipitation
  • Cyclin-Dependent Kinase 9 / antagonists & inhibitors
  • Cyclin-Dependent Kinase 9 / metabolism
  • Cyclin-Dependent Kinase 9 / physiology*
  • Dactinomycin / pharmacology
  • Dichlororibofuranosylbenzimidazole / pharmacology
  • Flavonoids / pharmacology
  • Histones / metabolism*
  • Humans
  • Mice
  • Nucleic Acid Synthesis Inhibitors / pharmacology
  • Piperidines / pharmacology
  • RNA, Messenger / metabolism*
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / physiology
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / physiology
  • Ubiquitination / genetics

Substances

  • Flavonoids
  • Histones
  • Nucleic Acid Synthesis Inhibitors
  • Piperidines
  • RNA, Messenger
  • Dactinomycin
  • alvocidib
  • Dichlororibofuranosylbenzimidazole
  • RNF20 protein, human
  • RNF40 protein, human
  • Ubiquitin-Protein Ligases
  • Cyclin-Dependent Kinase 9